Our objectives are: (1) To answer important but unresolved questions concerning chenodeoxycholic (cheno) therapy which are not addressed by the National Cooperative Gallstone Study, which should be answered before cheno will have broad applicability and acceptance, and which we are well-suited to answer because of our patient population and longstanding interest in gallstone disease. Specifically, we will study: a) the efficacy and safety (liver function, serum lipids, colonic histology) of optimum dose, long-term, cheno-therapy in radiolucent and partially calcified gallstones and biliary duct stones; b) the rate and determining factors of gallstone recurrence after discontinuing cheno-therapy; and c) the prophylactic potential of low dose, cheno in comparison to a high fiber diet and a before-bed snack. (2) To apply our well-established expertise in clinical and basic bile acid research to an in-depth evaluation of ursodeoxycholic (urso) acid. Specifically, we will study: a) the efficacy and safety of urso relative to cheno in situations where cheno-therapy is less than ideal (partially calcified gallstones, obesity and post-ileectomy saturated bile); and b) the effect of urso on primary bile acid kinetics, biliary lipid secretion, and cholesterol absorption and kinetics. (3) To continue our evaluation of novel litholytic agents for the dissolution of biliary duct stones by intraductal perfusion. Specifically, studies will include: a) continuation of the clinical evaluation of the medium chain monoglyceride, mono-octanoin; and b) the systematic evaluation in vitro of parameters (altered viscosity and emulsion formation) which might influence its solvent characteristics. (4) To utilize the combination of clinical investigative expertise and basic science skills wich characterize our group for the development and/or application of novel methodology for bile acid research. Specificially, studies will include: a) the synthesis of deuterated bile acids and application of the kinetic isotope effect to the study of bile acid metabolism; b) the synthesis of fluroescent bile acids and their application to the study of bile acid metabolism; and c) the application of radio-labelled cellulose and lignin to the in vitro study of biliary lipid-bran interactions.